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Biomedical subjects

R R Roy

Publications and source records attributed to R R Roy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Retraining the injured spinal cord.

The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

Animals↗
PubMed2001

Temporal effects of inactivty on myosin heavy chain gene expression in rat slow muscle.

Myosin heavy chain (MHC) mRNA and protein profiles in adult rat soleus and adductor longus were determined after 4, 8, 15, 30, 60, and 90 days of spinal cord isolation (SI). SI results in complete neuromuscular inactivity while leaving the motoneuron-muscle fiber connections intact. From 15 to 90 days, type I MHC mRNA was significantly decreased, whereas type I MHC protein did not significantly decrease until 30 and 60 days in the soleus and adductor longus, respectively. However, in both muscles, slow MHC downregulation was offset by significant upregulation of the faster MHC isoforms, primarily IIx. From 60 to 90 days, type I MHC was almost completely replaced with faster isoforms at the mRNA and protein levels. Thus, chronic inactivity and unloading of slow rat hindlimb muscles shifted the MHC profile from predominately type I to type IIx MHC mRNA and protein.

Animals↗
PubMed2001

Role of motor unit structure in defining function.

Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge.

Animals↗
PubMed2001

Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle.

We have investigated the impact of neuromuscular activity on the expression of neurotrophins in the lumbar spinal cord region and innervating skeletal muscle of adult rats. Rats were exercised on a treadmill for 1 day or 5 consecutive days and euthanized at 0, 2 or 6 h after the last bout of exercise. By Day 1, there was no clear evidence of an increase in brain-derived neurotrophic factor (BDNF) mRNA in the spinal cord or the soleus muscle. By Day 5, there was a significant increase in BDNF mRNA in the spinal cord at 2 h post-training, and the soleus muscle showed a robust increase between 0 and 6 h post-training. Immunoassays showed significant increases in BDNF protein in the soleus muscle by training Day 5. Immunohistochemical analyses showed elevated BDNF levels in motoneuron cell bodies and axons in the ventral horn. Neurotrophin-3 (NT-3) mRNA was measured to determine whether selected neurotrophins respond with a selective pattern of induction to neuromuscular activity. In the spinal cord, there was a progressive post-training decrease in NT-3 mRNA following a single bout of training, while there was a significant increase in NT-3 mRNA at 2 h post-training by Day 5. The soleus muscle showed a progressive increase in NT-3 mRNA by Days 1 and 5 following training. These results show that neuromuscular activity has specific effects on the BDNF and NT-3 systems, and that repetitive exercise affects the magnitude and stability of these responses.

Animals↗
PubMed2001

Expression of heat shock protein 72 in atrophied rat skeletal muscles.

Changes in the expression of heat shock protein 72 (HSP72) in response to atrophic-inducing perturbations of muscle involving chronic mechanical unloading and denervation were determined. Adult male Wistar rats were assigned randomly to a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN group. Tenotomy and DEN involved cutting the Achilles tendon and removing a segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P < 0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05). Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU + TEN group. Hind limb unloading alone had little effect on the HSP72 level in either muscle. Reduced levels of HSP72 were associated with a decreased soleus (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are responsive to a chronic decrease in the levels of loading and/or activation and suggest that the neuromuscular activity level and the presence of innervation of a muscle are important factors that induce HSP72 expression.

Achilles Tendon↗
PubMed2001

Ontogenetic, gravity-dependent development of rat soleus muscle.

We tested the hypothesis that rat soleus muscle fiber growth and changes in myosin phenotype during the postnatal, preweaning period would be largely independent of weight bearing. The hindlimbs of one group of pups were unloaded intermittently from postnatal day 4 to day 21: the pups were isolated from the dam for 5 h during unloading and returned for nursing for 1 h. Control pups were either maintained with the dam as normal or put on an alternating feeding schedule as described above. The enlargement of mass (approximately 3 times), increase in myonuclear number (approximately 1.6 times) and myonuclear domain (approximately 2.6 times), and transformation toward a slow fiber phenotype (from 56 to 70% fibers expressing type I myosin heavy chain) observed in controls were inhibited by hindlimb unloading. These properties were normalized to control levels or higher within 1 mo of reambulation beginning immediately after the unloading period. Therefore, chronic unloading essentially stopped the ontogenetic developmental processes of 1) net increase in DNA available for transcription, 2) increase in amount of cytoplasm sustained by that DNA pool, and 3) normal transition of myosin isoforms that occur in some fibers from birth to weaning. It is concluded that normal ontogenetic development of a postural muscle is highly dependent on the gravitational environment even during the early postnatal period, when full weight-bearing activity is not routine.

Age Factors↗
PubMed2001

Anabolic steroids increase exercise tolerance.

The influence of an anabolic androgenic steroid (AAS) on thymidine and amino acid uptake in rat hindlimb skeletal muscles during 14 days after a single exhaustive bout of weight lifting was determined. Adult male rats were divided randomly into Control or Steroid groups. Nandrolone decanoate was administered to the Steroid group 1 wk before the exercise bout. [3H]thymidine and [14C]leucine labeling were used to determine the serial changes in cellular mitotic activity, amino acid uptake, and myosin synthesis. Serum creatine kinase (CK) activity, used as a measure of muscle damage, increased 30 and 60 min after exercise in both groups. The total amount of weight lifted was higher, whereas CK levels were lower in Steroid than in Control rats. [3H]thymidine uptake peaked 2 days after exercise in both groups and was 90% higher in Control than in Steroid rats, reflecting a higher level of muscle damage. [14C]leucine uptake was approximately 80% higher at rest and recovered 33% faster postexercise in Steroid than in Control rats. In a separate group of rats, the in situ isometric mechanical properties of the plantaris muscle were determined. The only significant difference was a higher fatigue resistance in the Steroid compared with the Control group. Combined, these results indicate that AAS treatment 1) ameliorates CK efflux and the uptake of [3H]thymidine and enhances the rate of protein synthesis during recovery after a bout of weight lifting, all being consistent with there being less muscle damage, and 2) enhances in vivo work capacity and the in situ fatigue resistance of a primary plantarflexor muscle.

Anabolic Agents↗
PubMed2001

Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy.

Calcineurin (CaN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST.

Adaptation, Physiological↗
PubMed2001

Circadian force and EMG activity in hindlimb muscles of rhesus monkeys.

Continuous intramuscular electromyograms (EMGs) were recorded from the soleus (Sol), medial gastrocnemius (MG), tibialis anterior (TA), and vastus lateralis (VL) muscles of Rhesus during normal cage activity throughout 24-h periods and also during treadmill locomotion. Daily levels of MG tendon force and EMG activity were obtained from five monkeys with partial datasets from three other animals. Activity levels correlated with the light-dark cycle with peak activities in most muscles occurring between 08:00 and 10:00. The lowest levels of activity generally occurred between 22:00 and 02:00. Daily EMG integrals ranged from 19 mV/s in one TA muscle to 3339 mV/s in one Sol muscle: average values were 1245 (Sol), 90 (MG), 65 (TA), and 209 (VL) mV/s. The average Sol EMG amplitude per 24-h period was 14 microV, compared with 246 microV for a short burst of locomotion. Mean EMG amplitudes for the Sol, MG, TA, and VL during active periods were 102, 18, 20, and 33 microV, respectively. EMG amplitudes that approximated recruitment of all fibers within a muscle occurred for 5-40 s/day in all muscles. The duration of daily activation was greatest in the Sol [151 +/- 45 (SE) min] and shortest in the TA (61 +/- 19 min). The results show that even a "postural" muscle such as the Sol was active for only approximately 9% of the day, whereas less active muscles were active for approximately 4% of the day. MG tendon forces were generally very low, consistent with the MG EMG data but occasionally reached levels close to estimates of the maximum force generating potential of the muscle. The Sol and TA activities were mutually exclusive, except at very low levels, suggesting very little coactivation of these antagonistic muscles. In contrast, the MG activity usually accompanied Sol activity suggesting that the MG was rarely used in the absence of Sol activation. The results clearly demonstrate a wide range of activation levels among muscles of the same animal as well as among different animals during normal cage activity.

Animals↗
PubMed2001

Sensorimotor adaptations to microgravity in humans.

Motor function is altered by microgravity, but little detail is available as to what these changes are and how changes in the individual components of the sensorimotor system affect the control of movement. Further, there is little information on whether the changes in motor performance reflect immediate or chronic adaptations to changing gravitational environments. To determine the effects of microgravity on the neural control properties of selected motor pools, four male astronauts from the NASA STS-78 mission performed motor tasks requiring the maintenance of either ankle dorsiflexor or plantarflexor torque. Torques of 10 or 50% of a maximal voluntary contraction (MVC) were requested of the subjects during 10 degrees peak-to-peak sinusoidal movements at 0.5 Hz. When 10% MVC of the plantarflexors was requested, the actual torques generated in-flight were similar to pre-flight values. Post-flight torques were higher than pre- and in-flight torques. The actual torques when 50% MVC was requested were higher in- and post-flight than pre-flight. Soleus (Sol) electromyographic (EMG) amplitudes during plantarflexion were higher in-flight than pre- or post-flight for both the 10 and 50% MVC tasks. No differences in medial gastrocnemius (MG) EMG amplitudes were observed for either the 10 or 50% MVC tasks. The EMG amplitudes of the tibialis anterior (TA), an antagonist to plantarflexion, were higher in- and post-flight than pre-flight for the 50% MVC task. During the dorsiflexion tasks, the torques generated in both the 10 and 50% MVC tasks did not differ pre-, in- and post-flight. TA EMG amplitudes were significantly higher in- than pre-flight for both the 10 or 50% MVC tasks, and remained elevated post-flight for the 50% MVC test. Both the Sol and MG EMG amplitudes were significantly higher in-flight than either pre- or post-flight for both the 10 and 50% MVC tests. These data suggest that the most consistent response to space flight was an elevation in the level of contractions of agonists and antagonists when attempting to maintain constant torques at a given level of MVC. Also, the chronic levels of EMG activity in selected ankle flexor and extensor muscles during space flight and during routine activities on Earth were recorded. Compared with pre- and post-flight values, there was a marked increase in the total EMG activity of the TA and the Sol and no change in the MG EMG activity in-flight. These data indicate that space flight, as occurs on shuttle missions, is a model of elevated activation of both flexor and extensor muscles, probably reflecting the effects of programmed work schedules in flight rather than a direct effect of microgravity.

Adaptation, Physiological↗
PubMed2001

Is the recovery of stepping following spinal cord injury mediated by modifying existing neural pathways or by generating new pathways? A perspective.

The recovery of stepping ability following a spinal cord injury may be achieved by restoring anatomical connectivity within the spinal cord. However, studies of locomotor recovery in animals with complete spinal cord transection suggest that the adult mammalian spinal cord can acquire the ability to generate stepping after all descending input is eliminated and in the absence of neuronal regeneration. Moreover, rehabilitative gait training has been shown to play a crucial role in teaching existing spinal pathways to generate locomotion and appropriately respond to sensory feedback. This brief review presents evidence that neural networks in the mammalian spinal cord can be modulated pharmacologically and/or with task-specific behavioral training to generate weight-bearing stepping after a spinal injury. Further, the role that spinal learning can play in the management of humans with spinal cord injury is discussed in relation to interventions that are designed primarily to enhance neuronal regeneration.

Animals↗
PubMed2001

No effect of hypergravity on adult rat ventral horn neuron size or SDH activity.

BACKGROUND: Spaceflights of short duration (approximately 2 wk) result in adaptations in the size and/or metabolic properties of a select population of motoneurons located in the lumbosacral region of the rat spinal cord. A decrease in succinate dehydrogenase (SDH, an oxidative marker enzyme) activity of moderately sized (500-800 microm2) motoneurons in the retrodorsolateral region of the spinal cord (L6) has been observed after a 14-d flight. HYPOTHESIS: Our hypothesis was that exposure to short-term hypergravity would result in adaptations in the opposite direction, reflecting a continuum of morphological and biochemical responses in the spinal motoneurons from zero gravity to hypergravity. METHODS: Young, male rats were centrifuged at either 1.5 or 2.0 G for 2 wk. The size and SDH activity of a population of motoneurons in the retrodorsolateral region of the spinal cord (L5) were determined and compared with age-matched rats maintained at 1.0 G. The absolute and relative (to body weight) masses of the soleus, gastrocnemius, adductor longus and tibialis anterior muscles were compared among the three groups. RESULTS: There were no effects of either hypergravity intervention on the motoneuron properties. Rats maintained under hypergravity conditions gained less body mass than rats kept at 1.0 G. For the 1.5 and 2.0 G groups, the muscle absolute mass was smaller and relative mass similar to that observed in the 1.0 G rats, except for the adductor longus. The adductor longus absolute mass was similar to and the relative mass larger in both hypergravity groups than in the 1.0 G group. CONCLUSIONS: Our hypothesis was rejected. The findings suggest that rat motoneurons are more responsive to short-term chronic exposure to spaceflight than to hypergravity conditions.

Adaptation, Physiological↗
PubMed2001

Size and myonuclear domains in Rhesus soleus muscle fibers: short-term spaceflight.

The cross-sectional area (CSA), myonuclear number per mm of fiber length, and myonuclear domain (cytoplasmic volume/myonucleus) of mechanically isolated single fibers from biopsies of the soleus muscle of 5 vivarium control, 3 flight simulation and 2 flight (BION 11) Rhesus monkeys (Macaca [correction of Macacca] mulatta) were determined using confocal microscopy before and after a 14-day experimental period. Simulation monkeys were confined in chairs placed in capsules identical to those used during the flight. Fibers were classified as type I, type II or hybrid (containing both types I and II) based on myosin heavy chain (MHC) gel electrophoresis. A majority of the fibers sampled contained only type I MHC, i.e. 89, 62 and 68% for the control, simulation and flight groups, respectively. Most of the remaining fibers were hybrids, i.e. 8, 36 and 32% for the same groups. There were no significant pre-post differences in the fiber type composition for any of the experimental groups. There also were no significant pre-post differences in fiber CSA, myonuclear number or myonuclear domain. There was, however, a tendency for the fibers in the post-flight biopsies to have a smaller mean CSA and myonuclear domain (approximately 10%, p=0.07) than the fibers in the pre-flight biopsy. The combined mean cytoplasmic volume/myonucleus for all muscle fiber phenotypes in the Rhesus soleus muscle was approximately 25,000 micrometers3 and there were no differences in pre-post samples for the control and simulated groups. The cytoplasmic domains tended to be lower (p=0.08) after than before flight. No phenotype differences in cytoplasmic domains were observed. These data suggest that after a relatively short period of actual spaceflight, modest fiber atrophy occurs in the soleus muscle fibers without a concomitant change in myonuclear number.

Adaptation, Physiological↗
PubMed2000

How the science and engineering of spaceflight contribute to understanding the plasticity of spinal cord injury.

Space programs support experimental investigations related to the unique environment of space and to the technological developments from many disciplines of both science and engineering that contribute to space studies. Furthermore, interactions between scientists, engineers and administrators, that are necessary for the success of any science mission in space, promote interdiscipline communication, understanding and interests which extend well beyond a specific mission. NASA-catalyzed collaborations have benefited the spinal cord rehabilitation program at UCLA in fundamental science and in the application of expertise and technologies originally developed for the space program. Examples of these benefits include: (1) better understanding of the role of load in maintaining healthy muscle and motor function, resulting in a spinal cord injury (SCI) rehabilitation program based on muscle/limb loading; (2) investigation of a potentially novel growth factor affected by spaceflight which may help regulate muscle mass; (3) development of implantable sensors, electronics and software to monitor and analyze long-term muscle activity in unrestrained subjects; (4) development of hardware to assist therapies applied to SCI patients; and (5) development of computer models to simulate stepping which will be used to investigate the effects of neurological deficits (muscle weakness or inappropriate activation) and to evaluate therapies to correct these deficiencies.

Animals↗
PubMed2000

Increased expression of glutamate decarboxylase (GAD(67)) in feline lumbar spinal cord after complete thoracic spinal cord transection.

To determine changes in gamma-aminobutyric acid (GABA) in the spinal cord in response to a complete transection, we examined the cellular and tissue changes of the two forms of GABA synthetic enzyme glutamate decarboxylase (GAD(65) and GAD(67)). In situ hybridization, immunohistochemistry, and Western blot analyses show that spinal cord transection between thoracic segments 12 and 13 results in an increase of GAD(67), but not GAD(65), protein and mRNA in the lumbar spinal cord. This increase occurs mainly in the dorsal horn and persists for at least 12 months. In addition, there was relatively high GAD(67)-immunoreactivity around the central canal, with dorsolateral GAD(67)-immunoreactive fibers extending toward the ependyma and into the central canal in the transected animals. We suggest that an increase in GAD(67) leads to increased GABA production in spinal neurons below the injury site, resulting in altered inhibition and trophic support during posttrauma recovery and adaptation. Increased GABA synthesis around the central canal, in the vicinity of ependymal cells, may represent part of a regenerative process in the mammalian spinal cord, reminiscent of that observed in lower vertebrates.

Animals↗
PubMed2000

SDH activity and cell size of tibialis anterior motoneurons and muscle fibers in SAMP6.

Succinate dehydrogenase (SDH) activities and cross-sectional areas (CSAs) of tibialis anterior motoneurons and muscle fibers were determined in 20-, 40-, and 60-week-old male senescence-accelerated mice (SAMP6), and compared with those in age-matched accelerated-senescence resistant mice (SAMR1). The mean CSA of motoneurons in SAMP6 decreased at 60 weeks, primarily due to a selective loss of large (>400 microm2) motoneurons. The mean SDH activity of motoneurons with CSAs between 100 and 400 microm2 decreased in SAMP6, but not SAMR1, at 60 weeks. The mean muscle fiber SDH activities and CSAs in SAMP6 decreased at 60 weeks. There were no differences in the mean SDH activity or CSA of motoneurons or muscle fibers among 20-, 40-, and 60-week-old SAMR1. These results demonstrate that mice which have been shown to have a variety of accelerated-senescent features also have an earlier onset of age-related changes in motoneurons and the muscle fibers that they innervate when compared with age-matched accelerated-senescence resistant mice.

Age Factors↗
PubMed2000

Persistence of myosin heavy chain-based fiber types in innervated but silenced rat fast muscle.

Myosin heavy chain (MHC) profile and size of fibers in deep and superficial regions of the adult rat medial gastrocnemius (MG) were determined after 4, 15, 30, and 60 days of inactivity induced by spinal cord isolation (SI). After 4 days, fiber size decreased by 33 to 50% and 36 to 46% in deep and superficial regions, whereas MHC composition was unaffected. By 15 days, these values were 45 to 78% and 51 to 69%, and MHC composition was shifting toward faster isoforms. By 60 days, there were no pure type I MHC fibers and increases from 1 to 18% and 78 to 93% in pure type IIb fibers in deep and superficial regions. The percentage of type I MHC (gel electrophoresis) was approximately 10 and approximately 3%, and of type IIb approximately 40 and approximately 60% in control and 60-day SI rats. Thus, adaptations in the MHC molecule occurred at a slower rate and for a longer duration than the atrophic response.

Animals↗